There are drugs known which contain a low molecular weight active ingredient capable of creating an immunostimulating and/or immunorestorative effect. Most often levamisole hydrochloride and inosine benzoate are used at this time for such purposes.
Other active ingredients, such as NPT 15 392, i.e. erythro-9-(2-hydroxy-3-nonyl)hypoxanthine, also azimexone and ditiocarb are known to have immunomodulating, such as immunostimulating and immunorestorative effect. However, no medicinal drugs have yet been introduced, containing these active ingredients.
A standardization of known and new active ingredients, which stimulate and/or restore the immune system, is not readily possible at this time. This is due to the complexity of the immune system with its various regulatory and counterregulatory mechanisms and also to the absence of internationally agreed upon conditions for testing such agents in laboratory animals, and for clinical investigations of such agents in man. Furthermore, the aforementioned active ingredients are not available for marketing because they continue to be investigated to a greater extent with respect to their immunomodulating, immunostimulating and/or immunorestorative activity.
The difference in effect of the active ingredients on the various immunocompetent cells that react to, or are responsible for, an immune reaction also create a barrier towards a comprehensive comparability of compounds with immunostimulating and/or immunorestorative effect. These differences in effect do not permit uniform control of specific and nonspecific defense mechanisms. For example, levamisole hydrochloride has a predominantly immunorestorative effect in immunosuppressed organisms. Predominantly the T cells are stimulated, but with only a slight effect on the humoral response. Activation of nonspecific defence mechanisms is brought about by the stimulation of the hemocytophages, and the proliferation and bactericidal effect of macrophages. On the other hand, inosine benzoate manifests primarily an immunostimulating effect, among others, by an increase in the humoral immune response. The proliferation and differentiation of the T lymphocytes are also increased. The function of the macrophages is also increased through lymphokine induction.
Despite the progress in developing substances with immunomodulating, immunostimulating and/or immunorestoring activity, difficulties have been encountered in the few known methods in preparing such drugs. For example, the optical isomer of levamisole hydrochloride can be obtained by separating the diastereoisomer of the racemic tetramisole hydrochloride. The compound has a bitter, metallic taste, and after oral administration to man can result in vomiting, nausea, leucopenia, and agranulocytosis. Moreover, the physiological effect of levamisole hydrochloride is remarkably dependent on genetic factors, and the age and sex of the patient.
Inosine benzoate, which must be administered in relatively higher doses, such as about 50 mg/kg/day, can produce lead to vomiting, hyperuricemia and an increase in hematocrits. In the case of azimexone, headaches, vomiting and a decrease in haemoglobin (Hb) and erythrocytes are observed as side effects.
Therefore there is a need for drugs for the treatment of diseases of the immune system and/or for the treatment of virus infections in man and animals, as well as for methods for their preparation. There is a particular need for new drugs with immunomodulating, such as immunostimulating and/or immunorestorative action for man and animals, having improved specific and nonspecific defensive protective activity.